Analysis of differentially changed gene expression in EA.hy926 human endothelial cell after exposure of fine...

Epidemiological studies have illustrated that PM2.5 is closely related to cardiovascular disease (CVD), but underlying toxicological mechanisms are not yet clear. The main purpose of this study is to disclose the potential biological mechanisms responsible for PM2.5-dependent adverse cardiovascular outcomes through the appliance of genome-wide transcription microarray. From results, compared with the control group, there are 97 genes significantly altered in 2.5 μg/cm² PM2.5 treated group and 440 differentially expressed genes in 10 μg/cm² group. Of note, when 2.5 μg/cm² and 10 μg/cm² group were respectively compared with the control group, 46 significantly altered genes showed a consistent tendency in two treated groups, of which 31 genes were upregulated while 15 genes were meanwhile downregulated. Based on Gene Ontology (GO) annotation, altered genes are mainly gathered in functions of cellular processes and immune regulation. Pathway analysis indicated that TNF signaling pathway, NOD-like receptor (NLRs) signaling pathway, MAPK signaling pathway and gap junction are vital pathways involved in PM2.5-induced toxicity in EA.hy926. Moreover, results from RT-qPCR further corroborated that changed genes are implicated in oxidative stress, inflammation and metabolic disorder. In addition, metabolism of xenobiotics by cytochrome P450 pathway is the critical pathway which may serve as a target to prevent PM2.5-induced CVD. To sum up, our effort provides a fundamental data for further studies regarding mechanisms of PM2.5-induced cardiovascular toxicity on the basis of genome-wide screening.